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Background: Garcinia brasiliensis is traditionally known for its medicinal properties. Objectives: Here, we investigated the effects of crude extract (CE) and ethyl acetate fraction (EAF) obtained from G. brasiliensis leaves on the ascitic (EA) and solid (ES) forms of Ehrlich tumors. Methods: Induced and uninduced BALB/c mice were treated intramuscularly, for 7 or 14 days, with saline solution or CE and EAF, both at a 10% concentration, based on in vitro cytotoxicity assessment. Biochemical analyses were also performed to evaluate in vivo cytotoxicity. In relation to tumor-induced animals, morphological changes, plasma enzymes, inflammatory mediators and the induction of apoptosis were analyzed, in addition to histopathological studies, to evaluate the inhibition of tumor growth. Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) were regulated by CE and EAF administration. Furthermore, both treatments were effective in inhibiting tumor growth in EA and ES by modulating the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, decreasing mast cells numbers and inducing apoptosis. Conclusions: This research indicates that both CE and EAF from G. brasiliensis leaves have potential antitumor effects with low cytotoxicity. [ABSTRACT FROM AUTHOR]

Conjoined twins (CTs), popularly referred to as Siamese twins, are a rare anomaly due to monochorionic and monoamniotic twin pregnancies. Dicephalus dibrachius dipus, a type of parapagus conjoined twin which is characterized by possessing two arms, two legs, a single trunk and two heads, epidemiologically, is an even rarer occurrence of CTs. In this article, a rare, well-preserved anatomical specimen of a dicephalus dibrachius dipus conjoined twin is presented. This study was conducted in a specimen which is part of the collection of the Embryology Museum of the institution by donation and approved by the Research Ethics Committee (REC). The female conjoined twins were born at full-term by cesarean section in the 1970s and died hours after birth. A thorough anatomical description was made through observational analysis, computed tomography and 3D reconstructed images. Major abnormalities were observed in the cardiovascular, respiratory and digestive systems. The internal anatomy exhibited a heart with three atria, two ventricles, two aortic arches, two pulmonary arteries, one innominate venous trunk and a respiratory system with two tracheas and four lungs. No other report was similar to our three atria heart description. This article provides a thorough anatomical description of all systems, which is valuable information for further studies on CTs. [ABSTRACT FROM AUTHOR]

Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine‐disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX‐2 and p‐STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor‐alpha and transforming growth factor‐beta 1 (TGF‐β1). Increase of tumor‐associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro‐tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA‐exposed MG. Tryptase‐positive MCs increased in disrupted MG and expressed TGF‐β1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile. [ABSTRACT FROM AUTHOR]

The endothelial cells' dysfunction linked to the development of atherosclerosis plays an important role in the regulation of inflammatory responses. Previous studies demonstrated the antiatherogenic effects of Garcinia kola seed extracts based on their lipid lowering effects. Our recent studies showed the in vitro antioxidant and anti-inflammatory activities of the ethanolic extract of Garcinia kola stem barks (EE). For more insight on the antiatherogenic effect of EE, we investigated its activity on some key points of the atherosclerosis process. The cytotoxicity of EE as well as its effects on LDL-uptake, LPS-induced InterCellular Adhesion Molecule (ICAM-1) and Annexin-1 (Anxa-1) expression and LPSinduced DNA damage were evaluated in Human Umbilical Vein Endothelial Cells (HUVECs). EE significantly (p<0.0001) increased the cell viability in both naive and LPS-treated HUVECs. At the concentrations of 50 and 100 µg/ml, EE significantly reduced LDL-uptake by endothelial cells stimulated with LPS. The immunohistochemistry results showed a significant (p<0.01) decrease in the ICAM-1 expression at the EE concentration of 250 µg/ml. EE also showed a significant (p<0.0001) concentration-dependent reduction of Annexin-1 expression in LPS-treated HUVECs. Besides, EE exhibited significant inhibition on LPS-induced genotoxicity marked by a decrease in tail DNA expression (p<0.0001) and tail movement expression (p<0.001) for the concentrations of 50 and 100 µg/ml. These findings showed that EE may mitigate the atherogenic process by reducing LDL-uptake and the expression of adhesion molecules. Thus, the EE of Garcinia kola turns out to be a potential candidate for the treatment of atherosclerosis with a lower risk of toxicity. [ABSTRACT FROM AUTHOR]

Verbena officinalis L. or vervain is an herbal medicine and dietary supplement used worldwide. It is used for antidepressant and anticonvulsant purposes, as well as to treat inflammatory disorders, skin burns, abrasions, and gastric diseases, among others. Here, we investigated the biochemical, antioxidant, and histopathological effects of vervain against chronic physical stress. Male Wistar rats were submitted to chronic physical training and oral administration of 200 mg/kg of extract for 7 weeks. Control animals were not treated with either stress or vervain. Body weight was monitored during the study. Liver, kidney, spleen, testis, epididymis, heart, skeletal muscle, and brain samples were collected. Blood cholesterol, lactate dehydrogenase (LDH), bilirubin, and creatinine kinase (CREA), among others, were studied. Glutathione peroxidase (GPox) and superoxide dismutase (SOD) antioxidant activity was analyzed in the blood, liver, and kidney. Testosterone measurements were also performed on whole testis extracts. We found significant weight ratios differences in the epididymis, brain, and heart. Animals submitted to training showed hemorrhagic livers. Kidney histology was affected by both stress and vervain. Cell disruption and vacuolization were observed in the testes and epididymis of animals submitted to stress. Hematological and biochemical markers as CREA, LDH, TP, CKI, URCA, γGT, and glucose revealed statistically significantly differences. Additionally, the activity of glutathione peroxide (GPox) and superoxide dismutase (SOD) in the blood was also impacted. Both stress and vervain have significant in vivo effects. Infusions of vervain include phenylpropanoids, iridoids, verbenalin, hastatoside, and flavonoids, amongst others, which interact synergistically to produce the preclinical effects reported here. [ABSTRACT FROM AUTHOR]

Acanthamoeba spp. can cause amoebic keratitis (AK). Chlorhexidine is effective for AK treatment as monotherapy, but with a relative failure on drug bioavailability in the deep corneal stroma. The combination of chlorhexidine and propamidine isethionate is recommended in the current AK treatment. However, the effectiveness of treatment depends on the parasite and virulence strains. This study aims to determine the potential of Garcinia mangostana pericarp extract and α-mangostin against Acanthamoeba triangularis, as well as the combination with chlorhexidine in the treatment of Acanthamoeba infection. The minimal inhibitory concentrations (MICs) of the extract and α-mangostin were assessed in trophozoites with 0.25 and 0.5 mg/mL, for cysts with 4 and 1 mg/mL, respectively. The MIC of the extract and α-mangostin inhibited the growth of A. triangularis trophozoites and cysts for up to 72 h. The extract and α-mangostin combined with chlorhexidine demonstrated good synergism, resulting in a reduction of 1/4–1/16 of the MIC. The SEM results showed that Acanthamoeba cells treated with a single drug and its combination caused damage to the cell membrane and irregular cell shapes. A good combination displayed by the extract or α-mangostin and chlorhexidine, described for the first time. Therefore, this approach is promising as an alternative method for the management of Acanthamoeba infection in the future. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) participate in all stages of skin healing and one of their mediators is the Annexin A1 protein (AnxA1), linked to inflammation, proliferation, migration and apoptosis processes, but not studied in thermal burns yet. Therefore, our objectives were to evaluate the behavior of MCs and AnxA1 in a second degree burn model, treated or not with silver sulfadiazine 1% (SDP 1%) and associated to macrophages quantification and cytokines dosages. MCs counts showed few cells in the early stages of repair but increased MCs in the final phases in the untreated group. The normal skin presented numerous tryptase-positive MCs that were reduced after burning in all analyzed periods. Differently, few chymase-positive MCs were observed in the early stages of healing, however, increased chymase-positive MCs were found at the final phase in the untreated group. MCs also showed high immunoreactivity for AnxA1 on day 3 in both groups. In the tissue there was a strong protein expression in the early stages of healing, but in the final phases only in the SDP treated animals. TNF-α, IL-1β, IL-6, IL-10 and MCP-1 levels and macrophages quantification were increased in inflammation and reepithelialization phases. Reduced IL-1β, IL-6 and IL-10 levels and numerous macrophages occurred in the treated animals during tissue repair. Our results indicate modulation in the profile of MCs and AnxA1expression during healing by the treatment with SDP 1%, pointing them as targets for therapeutic interventions on skin burns. [ABSTRACT FROM AUTHOR]

The incidence of penile cancer varies between populations but is rare in developed nations. Penile cancer is associated with a number of established risk factors and associated diseases including phimosis with chronic inflammation, human papillomavirus (HPV) infection, poor hygiene and smoking. The objective of this study was to identify genes related to this type of cancer. The detection of HPV was analyzed in 47 penile squamous cell carcinoma samples. HPV DNA was detected in 48.9% of penile squamous cell carcinoma cases. High-risk HPV were present in 42.5% of cases and low-risk HPV were detected in 10.6% of penile squamous cell carcinomas. The RaSH approach identified differential expression of Annexin A1 (ANXA1), p16, RPL6, PBEF1 and KIAA1033 in high-risk HPV positive penile carcinoma; ANXA1 and p16 were overexpressed in penile squamous cells positive for high-risk HPVs compared to normal penile samples by qPCR. ANXA1 and p16 proteins were significantly more expressed in the cells from high-risk HPV-positive penile carcinoma as compared to HPV-negative tumors (p<0.0001) independently of the subtype of the carcinoma. Overexpression of ANXA1 might be mediated by HPV E6 in penile squamous cell carcinoma of patients with high-risk HPVs, suggesting that this gene plays an important role in penile cancer. [ABSTRACT FROM AUTHOR]

Objectives To establish the role and effect of glucocorticoids and the endogenous annexin A1 (AnxA1) pathway in inflammatory arthritis. Methods Ankle joint mRNA and protein expression of AnxA1 and its receptors were analysed in naive and arthritic mice by real-time PCR and immunohistochemistry. Inflammatory arthritis was induced with the K/BxN arthritogenic serum in AnxA1+/+ and AnxA1-/- mice; in some experiments, animals were treated with dexamethasone (Dex) or with human recombinant AnxA1 or a protease-resistant mutant (termed SuperAnxA1). Readouts were arthritic score, disease incidence, paw oedema and histopathology, together with pro-inflammatory gene expression. Results All elements of the AnxA1 pathway could be detected in naive joints, with augmentation during ongoing disease, due to the infiltration of immune cells. No difference in arthritis intensity of profile could be observed between AnxA1+/+ and AnxA1-/- mice. Treatment of mice with Dex (10 µg intraperitoneally daily from day 2) afforded potent antiarthritic effects highly attenuated in the knockouts: macroscopic changes were mirrored by histopathological findings and pro-inflammatory gene (eg, Nos2) expression. Presence of proteinase 3 mRNA in the arthritic joints led the authors to test AnxA1 and the mutant SuperAnxA1 (1 µg intraperitoneally daily in both cases from day 2), with the latter one being able to accelerate the resolving phase of the disease. Conclusion AnxA1 is an endogenous determinant for the therapeutic efficacy of Dex in inflammatory arthritis. Such an effect can be partially mimicked by application of SuperAnxA1 which may represent the starting point for novel antiarthritic therapeutic strategies. [ABSTRACT FROM AUTHOR]

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Veterinary Science is the property of Archives of Veterinary Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Veterinary Science is the property of Archives of Veterinary Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Deregulation of VEGFA (Vascular Endothelial Growth Factor A) and NFE2L2 (Nuclear Factor (Erythroid-derived 2)-Like 2), involved in angiogenesis and oxidative stress, can lead to thyroid cancer progression. MiR-17-5p and miR-612 are possible regulators of these genes and may promote thyroid disorders. In order to evaluate the involvement of VEGFA, NFE2L2, hsa-miR-17-5p, and hsa-miR-612 in thyroid pathology, we examined tissue samples from colloid goiter, papillary thyroid cancer (PTC), and a normal thyroid. We found higher levels of VEGFA and NFE2L2 transcripts and the VEGFA protein in goiter and PTC samples than in normal tissue. In the goiter, miR-612 and miR-17-5p levels were lower than those in PTC. Tumors, despite showing lower VEGFA mRNA expression, presented higher VEGFA protein levels compared to goiter tissue. In addition, NRF2 (Nuclear Related Transcription Factor 2) protein levels in tumors were higher than those in goiter and normal tissues. Inhibition of miR-17-5p resulted in reduced NFE2L2 expression. Overall, both transcript and protein levels of NFE2L2 and VEGFA were elevated in PTC and colloid goiter. Hsa-miR-612 showed differential expression in PTC and colloid goiter, while hsa-miR-17-5p showed differential expression only in colloid goiter, suggesting that hsa-miR-17-5p may be a positive regulator of NFE2L2 expression in PTC. [ABSTRACT FROM AUTHOR]